| Codeine phosphate hemihydrate |
| CAS No. : 41444-62-6 |
History
Codeine is an alkaloid found in opium and other poppy saps like Papaver bracteatum, the Iranian poppy, in concentrations ranging from 0.3 to 3.0 percent. While codeine can be extracted from opium, most codeine is synthesized from morphine through the process of O-methylation. It was first isolated in 1832 in France by Jean-Pierre Robiquet.
The effects of the Nixon War On Drugs by 1972 or so had caused across-the-board shortages of illicit and licit opiates because of a scarcity of natural opium, poppy straw and other sources of opium alkaloids, and the geopolitical situation was getting less helpful for the United States. After a large percentage of the opium and morphine in the US National Stockpile of Strategic & Critical Materials had to be tapped in order to ease severe shortages of medicinal opiates—the codeine-based antitussives in particular—in late 1973, researchers were tasked with and quickly succeeded in finding a way to synthesize codeine and its derivatives and precursors from scratch from petroleum or coal tar using a process developed at the United States' National Institutes of Health.
SIDE EFFECTS
The most frequent adverse reactions include lightheadedness, dizziness, sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in non ambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down.
Other adverse reactions include euphoria, dysphoria, constipation, and pruritus.
Drug Abuse and Dependence
Controlled Substance: Codeine phosphate is a Schedule II narcotic.
Dependence
Although much less potent in this regard than morphine, codeine can produce drug dependence a.d. therefore, has the potential for being abused. Patients given 60 mg codeine every 6 hours for 2 months usually show some tolerance and mild withdrawal symptoms. Development of the dependent state is recognized by an increased tolerance to the analgesic effect and the appearance of purposive phenomena (complaints, pleas, demands, or manipulative actions) shortly before the time of the next scheduled dose. A patient in withdrawal should be treated in a hospital environment. Usually, it is necessary only to provide supportive care with administration of a tranquilizer to suppress anxiety. Severe symptoms of withdrawal may require administration of a replacement narcotic.
INTERACTION
Carbamazepine, hydantoins, sulfinpyrazone
May result in increased risk of hepatotoxicity.
Cimetidine
Effects of codeine may be enhanced, increasing toxicity.
CNS depressants (eg, barbiturates, ethyl alcohol, other narcotics)
May result in additive CNS depressant effects and toxicity.
Tricyclic antidepressants, phenothiazines
May cause additive CNS depressant effects and toxicity.
Laboratory Test Interactions
With Chemstrip bG , Dextrostix , and Visidex II home blood glucose systems, drug may cause false decrease in mean glucose values. False-positive results may occur in urinary 5-hydroxy-indoleacetic acid test.
USES: This medication is used to treat mild to moderately severe pain. Codeine phosphate is a narcotic pain reliever. It acts on certain centers in the brain to give you pain relief.
Relation to other opiates
Codeine is the starting material and prototype of a large class of mainly mild to moderately strong opioids such as hydrocodone, dihydrocodeine and its derivatives such as nicocodeine. Other series of codeine derivatives include isocodeine and its derivatives, which were developed in Germany starting around 1920. Related to codeine in other ways are Codeine-N-Oxide (Genocodeine), related to the nitrogen morphine derivatives as is codeine methobromide, and heterocodeine which is a drug six times stronger than morphine and 72 times stronger than codeine due to a small re-arrangement of the molecule, viz. moving the methyl group from the 3 to the 6 position on the morphine carbon skeleton. Drugs bearing resemblance to codeine in effects due to close structural relationship are variations on the methyl groups at the 3 position including ethylmorphine a.k.a. codethyline (Dionine) and benzylmorphine (Peronine). While having no narcotic effects of its own, the important opioid precursor thebaine differs from codeine only slightly in structure. Pseudocodeine and some other similar alkaloids not currently used in medicine are found in trace amounts in opium as well.
Recreational use
Codeine can be used as a recreational drug. However, it has much less abuse potential than some other opiates or opioids, such as oxycodone and hydrocodone.
In some countries, cough syrups and tablets containing codeine are available without prescription; some potential recreational users are reported to buy codeine from multiple pharmacies so as not to arouse suspicion. A heroin addict may use codeine to ward off the effects of a withdrawal.
Codeine is also available in conjunction with the anti-nausea medication promethazine in the form of a syrup. Brand named as Phenergan with Codeine or generically as promethazine with codeine this medication is quickly becoming one of the most highly abused codeine preparations.
Codeine is also demethylated by reaction with pyridine to illicitly synthesize morphine. Pyridine is toxic and possibly carcinogenic, so morphine illicitly produced in this manner (and potentially contaminated with pyridine) may be particularly harmful. Codeine can also be turned into α-chlorodide which is used in the clandestine synthesis of desomorphine (Permonid). Codeine can also be turned directly into stronger derivatives of the dihydrocodeine and hydrocodone families and a few others with various chemicals and equipment.
Codeine is an alkaloid obtained from opium or prepared from morphine by methylation and occurs as white crystals. Codeine effloresces slowly in dry air and is effected by light. The chemical name of codeine phosphate is 7,8-Didehydro-4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha-ol phosphate (1:1)(salt) hemihydrate and has the empirical formula of C18H21NO3•H3PO4•1/2H20. Its molecular weight is 406.4.
Each soluble tablet contains 30 mg (0.074 mmol) or 60 mg (0.15 mmol) of codeine phosphate. These tablets also contain lactose and sucrose.
Soluble tablets of codeine phosphate are freely soluble in water. They are intended for the preparation of solutions for parenteral administration. These tablets are not sterile. Codeine phosphate is an analgesic.
For Analgesia: Dosage should be adjusted according to the severity of the pain and the response of the patient.
Adults: 15 to 60 mg every 4 to 6 hours (usual adult dose, 30 mg).
Children: 1 Year of Age and Older - 0.5 mg/kg of b.d. weight or 15 mg/m2 of b.d. surface every 4 to 6 hours.
Soluble tablets codeine phosphate are administered subcutaneously or intramuscularly.
Solutions for injection should be prepared with sterile water and filtered through a 0.22 membrane filter.
Codeine in combination with other narcotic analgesics, general anesthetics, phenothiazines, tranquilizers, sedative-hypnotics, or other CNS depressants (including alcohol) has additive depressant effects. When s.c. combination therapy is contemplated, the dosage of one or both agents should be reduced.
Head Injury and Increased Intracranial Pressure: The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal-fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a preexisting increase in intracranial pressure. Furthermore, narcotics produce adverse reactions that may obscure the clinical course in patients with head injuries.
Acute Abdominal Conditions: The administration of codeine or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
Special-Risk Patients: Codeine should be given with caution to certain patients, s.c. as the elderly or debilitated and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, and prostatic hypertrophy or urethral stricture.
Kidney or Liver Dysfunction: Codeine phosphate may have a prolonged cumulative effect in patients with kidney or liver dysfunction.
Information for the Patient
Codeine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, s.c. as driving a car or operating machinery. Codeine in combination with other narcotic analgesics, phenothiazines, sedative hypnotics, and alcohol has additive depressant effects.
Pregnancy
Pregnancy Category C Animal reproduction studies have not been conducted with codeine phosphate. It is also not known whether codeine phosphate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. On the basis of the historical use of codeine phosphate during all stages of pregnancy, there is no known risk of fetal abnormality. Codeine phosphate should be given to a pregnant woman only if clearly needed.
Labor and Delivery
The use of codeine phosphate in obstetrics may prolong labor. It passes the placental barrier and may produce depression of respiration in the newborn. Resuscitation a.d. in severe depression, the administration of naloxone may be required.
Someone told me today that Sopadeine Max is the UK version of hydrocodone. Has anyone heard of it? To me it just look like codeine with caffeine. Am I wrong? Does anyone know about "Codeine phosphate hemihydrate."
NO. It is an over the counter product in the UK and contains 12.8 mg of codeine. That is less than a Tylenol 2 here, which would most likely be prescribed for children or people very sensitive to codeine or narcotic pain relievers. Nice to have though for those times you need something just a bit more effective than aspirin or ibuprofen or tylenol, but don't need the moderately powerful hydrocodone. Unfortunately, here in the US, even a trace amount of codeine in anything would make it a schedule III controlled substance just like a vicodin or norco. But most English speaking countries around the world makes available OTC small dose codeine pain relievers. Things like that should be available here also, but there isn't even a hint of seeing that any day soon. Really too bad. But I don't know if hydrocodone is even available in the UK.
Medicine Name Active Ingredients/Generics Company Name Last eMC Update
Boots Paracetamol and Codeine Extra Capsules
paracetamol, caffeine, codeine phosphate hemihydrate BOOTS COMPANY PLC
13-Jan-09
Cuprofen Plus
ibuprofen, codeine phosphate hemihydrate SSL International plc 06-Mar-08
Panadol Ultra
paracetamol, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
15-Jun-07
Paracetamol and Codeine Caplets (Boots Company plc)
paracetamol, codeine phosphate hemihydrate BOOTS COMPANY PLC
15-Aug-08
Solpadeine Max
paracetamol, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
15-Jun-07
Solpadeine Migraine Ibuprofen & Codeine Tablets
ibuprofen, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
21-Jun-07
Solpadeine Plus Capsules
paracetamol, caffeine, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
18-Mar-09
Solpadeine Plus Soluble Tablets
paracetamol, caffeine, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
18-Mar-09
Solpadeine Plus Tablets
paracetamol, caffeine, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
18-Mar-09
Solpadol Capsules, Solpadol Effervescent Tablets, Solpadol Caplets
paracetamol, codeine phosphate hemihydrate sanofi-aventis
14-May-09
A real world approach to drugs: many drug interactions, side effects, or effectivenesses can not be detected when drugs are approved. They may be found only after the drugs have been used by millions of people and for a long time. Large, long term drug studies are able to discover these real world drug outcomes.
Comparison with the patient's adverse outcomes:
Name Count (% of total reports)
Abdominal Pain Upper 12 (1.76%)
Lipase Increased 1 (0.15%)
Neutrophil Count Decreased 4 (0.59%)
White Blood Cell Count Decreased 11 (1.61%)
^Back to Content
Top overall drug interactions, adverse side effects:
Name Count (% of total reports)
1 Nausea 50 (7.33%)
2 Drug ineffective 45 (6.60%)
3 Fall 43 (6.30%)
4 Fatigue 38 (5.57%)
5 Chest pain 36 (5.28%)
6 Pyrexia 34 (4.99%)
7 Anxiety 32 (4.69%)
8 Headache 31 (4.55%)
9 Depression 31 (4.55%)
10 Dizziness 31 (4.55%)
^Back to Content
Top long term (1+ years on drugs) drug interactions, side effects:
Name Count (% of total reports)
1 Hypertension 2 (14.29%)
2 Haematochezia 2 (14.29%)
3 Myocardial infarction 2 (14.29%)
4 Angina pectoris 2 (14.29%)
5 Oedema peripheral 2 (14.29%)
6 Microcytic anaemia 2 (14.29%)
7 Gastric cancer 2 (14.29%)
8 Gallbladder disorder 2 (14.29%)
9 Breast cancer 2 (14.29%)
10 Haematemesis 2 (14.29%)
Codeine is an alkaloid found in opium and other poppy saps like Papaver bracteatum, the Iranian poppy, in concentrations ranging from 0.3 to 3.0 percent. While codeine can be extracted from opium, most codeine is synthesized from morphine through the process of O-methylation. It was first isolated in 1832 in France by Jean-Pierre Robiquet.
The effects of the Nixon War On Drugs by 1972 or so had caused across-the-board shortages of illicit and licit opiates because of a scarcity of natural opium, poppy straw and other sources of opium alkaloids, and the geopolitical situation was getting less helpful for the United States. After a large percentage of the opium and morphine in the US National Stockpile of Strategic & Critical Materials had to be tapped in order to ease severe shortages of medicinal opiates—the codeine-based antitussives in particular—in late 1973, researchers were tasked with and quickly succeeded in finding a way to synthesize codeine and its derivatives and precursors from scratch from petroleum or coal tar using a process developed at the United States' National Institutes of Health.
SIDE EFFECTS
The most frequent adverse reactions include lightheadedness, dizziness, sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in non ambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down.
Other adverse reactions include euphoria, dysphoria, constipation, and pruritus.
Drug Abuse and Dependence
Controlled Substance: Codeine phosphate is a Schedule II narcotic.
Dependence
Although much less potent in this regard than morphine, codeine can produce drug dependence a.d. therefore, has the potential for being abused. Patients given 60 mg codeine every 6 hours for 2 months usually show some tolerance and mild withdrawal symptoms. Development of the dependent state is recognized by an increased tolerance to the analgesic effect and the appearance of purposive phenomena (complaints, pleas, demands, or manipulative actions) shortly before the time of the next scheduled dose. A patient in withdrawal should be treated in a hospital environment. Usually, it is necessary only to provide supportive care with administration of a tranquilizer to suppress anxiety. Severe symptoms of withdrawal may require administration of a replacement narcotic.
INTERACTION
Carbamazepine, hydantoins, sulfinpyrazone
May result in increased risk of hepatotoxicity.
Cimetidine
Effects of codeine may be enhanced, increasing toxicity.
CNS depressants (eg, barbiturates, ethyl alcohol, other narcotics)
May result in additive CNS depressant effects and toxicity.
Tricyclic antidepressants, phenothiazines
May cause additive CNS depressant effects and toxicity.
Laboratory Test Interactions
With Chemstrip bG , Dextrostix , and Visidex II home blood glucose systems, drug may cause false decrease in mean glucose values. False-positive results may occur in urinary 5-hydroxy-indoleacetic acid test.
USES: This medication is used to treat mild to moderately severe pain. Codeine phosphate is a narcotic pain reliever. It acts on certain centers in the brain to give you pain relief.
Relation to other opiates
Codeine is the starting material and prototype of a large class of mainly mild to moderately strong opioids such as hydrocodone, dihydrocodeine and its derivatives such as nicocodeine. Other series of codeine derivatives include isocodeine and its derivatives, which were developed in Germany starting around 1920. Related to codeine in other ways are Codeine-N-Oxide (Genocodeine), related to the nitrogen morphine derivatives as is codeine methobromide, and heterocodeine which is a drug six times stronger than morphine and 72 times stronger than codeine due to a small re-arrangement of the molecule, viz. moving the methyl group from the 3 to the 6 position on the morphine carbon skeleton. Drugs bearing resemblance to codeine in effects due to close structural relationship are variations on the methyl groups at the 3 position including ethylmorphine a.k.a. codethyline (Dionine) and benzylmorphine (Peronine). While having no narcotic effects of its own, the important opioid precursor thebaine differs from codeine only slightly in structure. Pseudocodeine and some other similar alkaloids not currently used in medicine are found in trace amounts in opium as well.
Recreational use
Codeine can be used as a recreational drug. However, it has much less abuse potential than some other opiates or opioids, such as oxycodone and hydrocodone.
In some countries, cough syrups and tablets containing codeine are available without prescription; some potential recreational users are reported to buy codeine from multiple pharmacies so as not to arouse suspicion. A heroin addict may use codeine to ward off the effects of a withdrawal.
Codeine is also available in conjunction with the anti-nausea medication promethazine in the form of a syrup. Brand named as Phenergan with Codeine or generically as promethazine with codeine this medication is quickly becoming one of the most highly abused codeine preparations.
Codeine is also demethylated by reaction with pyridine to illicitly synthesize morphine. Pyridine is toxic and possibly carcinogenic, so morphine illicitly produced in this manner (and potentially contaminated with pyridine) may be particularly harmful. Codeine can also be turned into α-chlorodide which is used in the clandestine synthesis of desomorphine (Permonid). Codeine can also be turned directly into stronger derivatives of the dihydrocodeine and hydrocodone families and a few others with various chemicals and equipment.
Codeine is an alkaloid obtained from opium or prepared from morphine by methylation and occurs as white crystals. Codeine effloresces slowly in dry air and is effected by light. The chemical name of codeine phosphate is 7,8-Didehydro-4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha-ol phosphate (1:1)(salt) hemihydrate and has the empirical formula of C18H21NO3•H3PO4•1/2H20. Its molecular weight is 406.4.
Each soluble tablet contains 30 mg (0.074 mmol) or 60 mg (0.15 mmol) of codeine phosphate. These tablets also contain lactose and sucrose.
Soluble tablets of codeine phosphate are freely soluble in water. They are intended for the preparation of solutions for parenteral administration. These tablets are not sterile. Codeine phosphate is an analgesic.
For Analgesia: Dosage should be adjusted according to the severity of the pain and the response of the patient.
Adults: 15 to 60 mg every 4 to 6 hours (usual adult dose, 30 mg).
Children: 1 Year of Age and Older - 0.5 mg/kg of b.d. weight or 15 mg/m2 of b.d. surface every 4 to 6 hours.
Soluble tablets codeine phosphate are administered subcutaneously or intramuscularly.
Solutions for injection should be prepared with sterile water and filtered through a 0.22 membrane filter.
Codeine in combination with other narcotic analgesics, general anesthetics, phenothiazines, tranquilizers, sedative-hypnotics, or other CNS depressants (including alcohol) has additive depressant effects. When s.c. combination therapy is contemplated, the dosage of one or both agents should be reduced.
Head Injury and Increased Intracranial Pressure: The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal-fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a preexisting increase in intracranial pressure. Furthermore, narcotics produce adverse reactions that may obscure the clinical course in patients with head injuries.
Acute Abdominal Conditions: The administration of codeine or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
Special-Risk Patients: Codeine should be given with caution to certain patients, s.c. as the elderly or debilitated and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, and prostatic hypertrophy or urethral stricture.
Kidney or Liver Dysfunction: Codeine phosphate may have a prolonged cumulative effect in patients with kidney or liver dysfunction.
Information for the Patient
Codeine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, s.c. as driving a car or operating machinery. Codeine in combination with other narcotic analgesics, phenothiazines, sedative hypnotics, and alcohol has additive depressant effects.
Pregnancy
Pregnancy Category C Animal reproduction studies have not been conducted with codeine phosphate. It is also not known whether codeine phosphate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. On the basis of the historical use of codeine phosphate during all stages of pregnancy, there is no known risk of fetal abnormality. Codeine phosphate should be given to a pregnant woman only if clearly needed.
Labor and Delivery
The use of codeine phosphate in obstetrics may prolong labor. It passes the placental barrier and may produce depression of respiration in the newborn. Resuscitation a.d. in severe depression, the administration of naloxone may be required.
Someone told me today that Sopadeine Max is the UK version of hydrocodone. Has anyone heard of it? To me it just look like codeine with caffeine. Am I wrong? Does anyone know about "Codeine phosphate hemihydrate."
NO. It is an over the counter product in the UK and contains 12.8 mg of codeine. That is less than a Tylenol 2 here, which would most likely be prescribed for children or people very sensitive to codeine or narcotic pain relievers. Nice to have though for those times you need something just a bit more effective than aspirin or ibuprofen or tylenol, but don't need the moderately powerful hydrocodone. Unfortunately, here in the US, even a trace amount of codeine in anything would make it a schedule III controlled substance just like a vicodin or norco. But most English speaking countries around the world makes available OTC small dose codeine pain relievers. Things like that should be available here also, but there isn't even a hint of seeing that any day soon. Really too bad. But I don't know if hydrocodone is even available in the UK.
Medicine Name Active Ingredients/Generics Company Name Last eMC Update
Boots Paracetamol and Codeine Extra Capsules
paracetamol, caffeine, codeine phosphate hemihydrate BOOTS COMPANY PLC
13-Jan-09
Cuprofen Plus
ibuprofen, codeine phosphate hemihydrate SSL International plc 06-Mar-08
Panadol Ultra
paracetamol, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
15-Jun-07
Paracetamol and Codeine Caplets (Boots Company plc)
paracetamol, codeine phosphate hemihydrate BOOTS COMPANY PLC
15-Aug-08
Solpadeine Max
paracetamol, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
15-Jun-07
Solpadeine Migraine Ibuprofen & Codeine Tablets
ibuprofen, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
21-Jun-07
Solpadeine Plus Capsules
paracetamol, caffeine, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
18-Mar-09
Solpadeine Plus Soluble Tablets
paracetamol, caffeine, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
18-Mar-09
Solpadeine Plus Tablets
paracetamol, caffeine, codeine phosphate hemihydrate GlaxoSmithKline Consumer Healthcare
18-Mar-09
Solpadol Capsules, Solpadol Effervescent Tablets, Solpadol Caplets
paracetamol, codeine phosphate hemihydrate sanofi-aventis
14-May-09
A real world approach to drugs: many drug interactions, side effects, or effectivenesses can not be detected when drugs are approved. They may be found only after the drugs have been used by millions of people and for a long time. Large, long term drug studies are able to discover these real world drug outcomes.
Comparison with the patient's adverse outcomes:
Name Count (% of total reports)
Abdominal Pain Upper 12 (1.76%)
Lipase Increased 1 (0.15%)
Neutrophil Count Decreased 4 (0.59%)
White Blood Cell Count Decreased 11 (1.61%)
^Back to Content
Top overall drug interactions, adverse side effects:
Name Count (% of total reports)
1 Nausea 50 (7.33%)
2 Drug ineffective 45 (6.60%)
3 Fall 43 (6.30%)
4 Fatigue 38 (5.57%)
5 Chest pain 36 (5.28%)
6 Pyrexia 34 (4.99%)
7 Anxiety 32 (4.69%)
8 Headache 31 (4.55%)
9 Depression 31 (4.55%)
10 Dizziness 31 (4.55%)
^Back to Content
Top long term (1+ years on drugs) drug interactions, side effects:
Name Count (% of total reports)
1 Hypertension 2 (14.29%)
2 Haematochezia 2 (14.29%)
3 Myocardial infarction 2 (14.29%)
4 Angina pectoris 2 (14.29%)
5 Oedema peripheral 2 (14.29%)
6 Microcytic anaemia 2 (14.29%)
7 Gastric cancer 2 (14.29%)
8 Gallbladder disorder 2 (14.29%)
9 Breast cancer 2 (14.29%)
10 Haematemesis 2 (14.29%)
No comments:
Post a Comment